Integrated functional and mass spectrometry-based flow cytometric phenotyping to describe the immune microenvironment in acute myeloid leukemia

Lamble, Adam J.; Dietz, Matthew S.; Laderas, Ted; McWeeney, Shannon K.; Lind, Evan F.

doi:10.1016/j.jim.2017.11.010

Cited by 13 publications

(8 citation statements)

References 63 publications

(60 reference statements)

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“…Immunophenotyping by CyTOF. Samples were stained for surface and intracellular molecules following protocols from Fluidigm, as detailed in SI Appendix, Supplemental Materials and Methods and as published in Lamble et al (77), and analyzed on a CyTOF 1 instrument. Two separate panels of antibodies were used for phenotyping (SI Appendix, Table S4).…”

Section: Methodsmentioning

confidence: 99%

Reversible suppression of T cell function in the bone marrow microenvironment of acute myeloid leukemia

Lamble

Kosaka

Laderas

et al. 2020

Proc. Natl. Acad. Sci. U.S.A.

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Acute myeloid leukemia (AML) is the most common acute leukemia in adults, with approximately four new cases per 100,000 persons per year. Standard treatment for AML consists of induction chemotherapy with remission achieved in 50 to 75% of cases. Unfortunately, most patients will relapse and die from their disease, as 5-y survival is roughly 29%. Therefore, other treatment options are urgently needed. In recent years, immune-based therapies have led to unprecedented rates of survival among patients with some advanced cancers. Suppression of T cell function in the tumor microenvironment is commonly observed and may play a role in AML. We found that there is a significant association between T cell infiltration in the bone marrow microenvironment of newly diagnosed patients with AML and increased overall survival. Functional studies aimed at establishing the degree of T cell suppression in patients with AML revealed impaired T cell function in many patients. In most cases, T cell proliferation could be restored by blocking the immune checkpoint molecules PD-1, CTLA-4, or TIM3. Our data demonstrate that AML establishes an immune suppressive environment in the bone marrow, in part through T cell checkpoint function.

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Section: Methodsmentioning

confidence: 99%

Reversible suppression of T cell function in the bone marrow microenvironment of acute myeloid leukemia

Lamble

Kosaka

Laderas

et al. 2020

Proc. Natl. Acad. Sci. U.S.A.

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“…The CyTOF data were analyzed on Cytobank 1 . Cell types were identified based on the following parameters: T cells, CD45+CD3+; B cells, CD45+CD19+; natural killer (NK) cells, CD45+CD3-CD16+CD56+ (19); monocytes, CD45+CD14+CD16+ (20); macrophages or microglia cells, CD45+CD11b+CD68+ (21); Tregs, CD45+CD4+CD25+CD127- (22); naïve CD4+ T cells, CD45+CD45RA+CCR7+CD4+ (23); and naïve CD8+ T cells, CD45+CD45RA+CCR7+CD8+ (23). Monocytes and macrophages constitute mononuclear phagocytes (24) (Supplementary Table S2).…”

Section: Cytof Data Analysismentioning

confidence: 99%

Single-Cell Atlas Reveals Complexity of the Immunosuppressive Microenvironment of Initial and Recurrent Glioblastoma

Wang

et al. 2020

Front. Immunol.

129

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The Glioblastoma (GBM) immune microenvironment plays a critical role in tumor development, progression, and prognosis. A comprehensive understanding of the intricate milieu and its interactions remains unclear, and single-cell analysis is crucially needed. Leveraging mass cytometry (CyTOF), we analyzed immunocytes from 13 initial and three recurrent GBM samples and their matched peripheral blood mononuclear cells (pPBMCs). Using a panel of 30 markers, we provide a high-dimensional view of the complex GBM immune microenvironment. Hematoxylin and eosin staining and polychromatic immunofluorescence were used for verification of the key findings. In the initial and recurrent GBMs, glioma-associated microglia/macrophages (GAMs) constituted 59.05 and 27.87% of the immunocytes, respectively; programmed cell death-ligand 1 (PD-L1), T cell immunoglobulin domain and mucin domain-3 (TIM-3), lymphocyte activation gene-3 (LAG-3), interleukin-10 (IL-10) and transforming growth factor-β (TGFβ) demonstrated different expression levels in the GAMs among the patients. GAMs could be subdivided into different subgroups with different phenotypes. Both the exhausted T cell and regulatory T (Treg) cell percentages were significantly higher in tumors than in pPBMCs. The natural killer (NK) cells that infiltrated into the tumor lesions expressed higher levels of CXC chemokine receptor 3 (CXCR3), as these cells expressed lower levels of interferon-γ (IFNγ). The immune microenvironment in the initial and recurrent GBMs displayed similar suppressive changes. Our study confirmed that GAMs, as the dominant infiltrating immunocytes, present great inter-and intratumoral heterogeneity and that GAMs, increased exhausted T cells, infiltrating Tregs, and nonfunctional NK cells contribute to local immune suppressive characteristics. Recurrent GBMs share similar immune signatures with the initial GBMs except the proportion of GAMs decreases.

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“…cytobank.org). The cell types were identified based on the following parameters: T cells, CD45+ CD3+; natural killer (NK) cells, CD45+ CD3-CD16+ CD56+ (10,19); B cells, CD45+ CD19+; monocytes, CD45+ CD14+ CD16+ 20; macrophages or microglial cells, CD45+ CD11b+ CD3-CD19-CD66b- (15); Tregs, CD45+ CD4+ CD25+ CD127- (21), and granulocytes, CD45+ CD66b+. Monocytes and macrophages constitute mononuclear phagocytes (22).…”

Section: Cytof Data Analysismentioning

confidence: 99%

High Dimensional Mass Cytometry Analysis Reveals Characteristics of the Immunosuppressive Microenvironment in Diffuse Astrocytomas

Wang

et al. 2020

Front. Oncol.

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The tumor immune microenvironment (TIME) plays a pivotal role in tumor development, progression, and prognosis. However, the characteristics of the TIME in diffuse astrocytoma (DA) are still unclear. Leveraging mass cytometry with a panel of 33 markers, we analyzed the infiltrating immune cells from 10 DA and 4 oligodendroglioma (OG) tissues and provided a single cell-resolution landscape of the intricate immune microenvironment. Our study profiled the composition of the TIME in DA and confirmed the presence of immune cells, such as glioma-associated microglia/macrophages (GAMs), CD8+ T cells, CD4+ T cells, regulatory T cells (Tregs), and natural killer cells. Increased percentages of PD-1+ CD8+ T cells, TIM-3+ CD4+ T cell subpopulations, Tregs and pro-tumor phenotype GAMs substantially contribute to the local immunosuppressive microenvironment in DA. DAs and OGs share similar compositions in terms of immune cells, while GAMs in DA exhibit more inhibitory characteristics than those in OG.

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Integrated functional and mass spectrometry-based flow cytometric phenotyping to describe the immune microenvironment in acute myeloid leukemia

Cited by 13 publications

References 63 publications

Reversible suppression of T cell function in the bone marrow microenvironment of acute myeloid leukemia

Reversible suppression of T cell function in the bone marrow microenvironment of acute myeloid leukemia

Single-Cell Atlas Reveals Complexity of the Immunosuppressive Microenvironment of Initial and Recurrent Glioblastoma

High Dimensional Mass Cytometry Analysis Reveals Characteristics of the Immunosuppressive Microenvironment in Diffuse Astrocytomas

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